CA3049981C

CA3049981C - Method for sterilizing a substrate having a hydrophilic coating and sterilized substrates

Info

Publication number: CA3049981C
Application number: CA3049981A
Authority: CA
Inventors: David J. Farrell; John P. O'mahony
Original assignee: Hollister Inc
Current assignee: Hollister Inc
Priority date: 2017-01-20
Filing date: 2018-01-19
Publication date: 2023-09-12
Anticipated expiration: 2038-01-19
Also published as: US20200038529A1; HUE056863T2; LT3570900T; EP3570900A1; HUE065416T2; CA3049981A1; DK3900752T3; ES2929334T3; WO2018136703A1; EP4088749B1; AU2018209951A1; AU2018209951B2; LT4088749T; EP3570900B1; ES2895272T3; EP3900752A1; DK3570900T3; LT3900752T; HUE060612T2; EP3900752B1

Abstract

A catheter assembly with a package defining a cavity. A medical device including a hydrophilic coating is located within the cavity. The hydrophilic coating includes a hydrophilic polymer and low molecular diacrylate, wherein the hydrophilic coating has been formed directly on an untreated surface of the medical device. A
wetting fluid including one or more non-polymeric polyols located within the cavity and in contact with the hydrophilic coating.

Description

METHOD FOR STERILIZING A SUBSTRATE HAVING
A HYDROPHILIC COATING AND STERILIZED SUBSTRATES
DESCRIPTION
Related Application [0001] The present application claims the benefit and priority of U.S.
Provisional Patent Application No. 62/448,733, filed January 20, 2017.
TECHNICAL FIELD

[0002] The present disclosure generally relates to methods for sterilizing a hydrophilically coated substrates using radiation, and more particularly, methods for radiation sterilization of hydrophilic coatings including a hydrophilic polymer and a low molecular weight diacrylate. The methods may include contacting the hydrophilic coating of a medical device with an aqueous solution containing one or more non-polymeric polyols and then exposing the medical device to radiation. The present disclosure also relates to sterilized hydrophilically coated medical devices, such as urinary catheters, and more particularly to ready-to-use sterilized hydrophilically coated medical device assemblies that include a package having therein a hydrophilically coated medical device and an aqueous solution containing a non-polymeric polyol, wherein the hydrophilic coating includes a hydrophilic polymer and a low molecular weight diacrylate oligomer.
BACKGROUND

[0003] It is known to coat medical devices, such as urinary catheters, with a hydrophilic coating. When the hydrophilic coating is wetted or hydrated with a wetting fluid, such as water, it becomes extremely lubricous which eases introduction of the device into the body and aids in reducing pain and discomfort associated with such introduction.

[0004] In some applications, the hydrophilically coated medical device is provided in a "dry" state wherein the user is required to wet the hydrophilic coating with a wetting fluid immediately prior to insertion into the body. In other applications, it is desirable to provide a hydrophilically coated medical device that is in a ready-to-use condition Date recue/Date received 2023-05-29 right out of the package. In the field of urinary catheters, a hydrophilically coated catheter may be provided in a catheter package wherein the catheter is stored in the package in contact with water so that the hydrophilic coating is wetted within the package and the catheter is ready for use right out of the package for the end user.

[0005] For various reasons, including but not limited to efficiency, effectiveness and cost, it is desirable to radiation sterilize packaged medical device assemblies. In some instances, the hydrophilically coated medical device and water are placed in the package and the package is sealed. After the package is sealed, the package having the hydrophilically coated medical device and water therein is exposed to radiation, such as gamma or [-Beam radiation, to sterilize the medical device.
It has been found, however, that sterilization of hydrophilic coatings in the hydrated state or while in contact with a wetting fluid can result in degradation of the coating or excessive crosslinking of the coating which can lead to an increase of coefficient of friction (decrease in lubricity) of the coating and/or cause instability of coating which may result in the coating undesirably detaching from the medical device prior to or during use.

[0006] Therefore, there remains a need for methods of sterilizing medical devices having hydrophilic coatings.
SUMMARY

[0007] There are several aspects of the present subject matter which may be embodied separately or together in the devices and systems described and claimed below. These aspects may be employed alone or in combination with other aspects of the subject matter described herein, and the description of these aspects together is not intended to preclude the use of these aspects separately.

[0008] In one aspect, a method for sterilizing a substrate, such as a medical device, having a hydrophilic coating that includes a hydrophilic polymer and a low molecular weight diacrylate compound wherein the method includes contacting the hydrophilic coating of the substrate with a wetting fluid containing one or more non-polymeric polyol and sterilizing the medical device by applying a sufficient amount of radiation while the device is in contact with the wetting fluid.

Date recue/Date received 2023-05-29

[0009] In another aspect, a catheter assembly includes a package defining a cavity.
A medical device including a hydrophilic coating is located within the cavity wherein the hydrophilic coating includes a hydrophilic polymer and a low molecular weight diacrylate compound. The assembly also includes a wetting fluid comprising one or more non-polymeric polyols is located within the cavity and in contact with the hydrophilic coating.
BRIEF DESCRIPTION OF DRAWINGS

[0010] Fig. 1 includes photographs of catheter tubes showing the visual results of the dye tests of Example 2.

[0011] Fig. 2 includes photographs of catheter tubes showing the visual results of the dye test of Example 3.

[0012] Fig. 3 includes a photograph of catheter tubes showing the visual results of the dye test of Comparative Example 1.
DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

[0013] The embodiments disclosed herein are for the purpose of providing a description of the present subject matter, and it is understood that the subject matter may be embodied in various other forms and combinations not shown in detail.
Therefore, specific embodiments and features disclosed herein are not to be interpreted as limiting the subject matter as defined in the accompanying claims.

[0014] The present disclosure relates to methods for sterilizing hydrophilically coated substrates, such as medical devices, using radiation wherein the hydrophilic coatings include a hydrophilic polymer and a low molecular weight diacrylate compound, such as a diacrylate oligomer. In one embodiment the diacrylate compound is polyethylene glycol diacrylate (PEGDA). Such methods may include bringing the hydrophilic coating of the medical device into contact with a wetting fluid for wetting the hydrophilic coating wherein the wetting fluid includes a wetting agent, such as liquid water, and one or more non-polymeric polyols. The hydrophilically coated medical device is then sterilized by applying a sufficient amount of radiation, such as gamma or E-Beam radiation.

Date recue/Date received 2023-05-29

[0015] Surprisingly, it has been found that the coefficient of friction can be kept low and the stability of a hydrophilic coating containing a low molecular weight diacrylate compound and a hydrophilic polymer can be maintained by adding non-polymeric polyols to the liquid for wetting a hydrophilic coating and that the non-polymeric polyols protect these properties during exposure to radiation for sterilization when wetted with such wetting fluids. It has been found that in irradiation sterilized hydrophilically coated devices that the combination of a hydrophilic coating containing a low molecular weight diacrylate compound and the use of a wetting fluid containing non-polymeric polyols can increase the stability and attachment of the coating to the surface of the substrate.

[0016] In some instances of applying hydrophilic coatings, the surface of the substrate is treated prior to forming a hydrophilic coating on the surface.
For example, the surface of a substrate of a urinary catheter may undergo a treatment, such as corona treatment, plasma treatment or the like or washing with a solvent, such ethanol or the like, to activate and/or clean the surface which can increase the affinity or attachment of the hydrophilic coating to the surface of the substrate. In other surface treatments, a primer or base layer is formed on the surface of the substrate wherein the primer or base layer acts a tie layer that has good attachment to both the surface of the substrate and of the hydrophilic surface.

[0017] Surprisingly, it has been found that a hydrophilic coating containing a low molecular weight diacrylate compound and a hydrophilic polymer can be formed directly on the surface of the substrate, without treating the surface of the substrate.
It has also been found that when such a coating is applied directly to the substrate and is radiation sterilized while in contact with a wetting fluid containing one or more non-polymeric polyols that coating has a strong adhesion to the substrate and maintains structural integrity.

[0018] The non-polymeric polyols contained in the wetting fluid may be, for example, 3-carbon sugar alcohols (Glycerol); 4-carbon sugar alcohols (Erythritol, Threitol); 5-carbon sugar alcohols (Arabitol, Xylitol, Adonitol) sugar alcohols, 6-carbon sugar alcohols (Mannitol, Sorbitol, Galactitol, Fucitol, lditol, Inositol), 7-carbon Date recue/Date received 2023-05-29 sugar alcohols (Volemitol),12-carbon sugar alcohols (Isomalt, Maltitol, Lactitol), 18-carbon sugar alcohols (Maltotriitol), and 24-carbon sugar alcohols (Maltotetraitol). In one embodiment, the wetting fluid includes water and glycerol.

[0019] The disclosure also relates to sterilized assemblies that may include a hydrophilically coated medical device and a wetting fluid for wetting the hydrophilic coating wherein the wetting fluid includes one or more non-polymeric polyols, the hydrophilic coating includes a hydrophilic polymer and a low molecular weight diacrylate and the hydrophilic coating has been formed on a treated or untreated surface of the medical device. The assemblies having been sterilized with radiation while the hydrophilic coating is in contact with the wetting fluid.

[0020] In one embodiment, the sterilized assembly includes a hydrophilically coated medical device, such as a urinary catheter having a hydrophilic coating thereon, and a wetting fluid including one or more non-polymeric polyols wherein the coated medical device and the wetting fluid are located in a sealed package and the assembly is exposed to radiation to sterilize the assembly and the medical device therein. In this embodiment, the hydrophilic coating of the medical device is wetted within the package and is maintained in a wetted state within the package, such that the medical device is in a ready-to-use condition right out of the package. In one embodiment, the catheter may be positioned in a sleeve that contains wetting fluid and the sleeve may be the package or the sleeve may be placed in an outer package. The sleeve may be, for example, a no-touch sleeve wherein the user uses the sleeve to insert the catheter. Furthermore, the hydrophilic coating may include a hydrophilic polymer and a low molecular weight diacrylate and the coating may be formed on a treated or untreated surface. Additionally, the package may be made of a substantially liquid and gas impermeable material so as to substantially limit the amount of or prevent the wetting fluid from escaping the package during storage, which may prolong the shelf life of the assembly.

[0021] By using wetting fluids that include a non-polymeric polyol and a hydrophilic coating made a hydrophilic polymer and low molecular diacrylates, it is possible to provide a hydrophilically coated medical device, such as a hydrophilically coated Date recue/Date received 2023-05-29 catheter, that is maintained in a wetted state by a wetting fluid within a package and has been radiation sterilized. Such a medical device is in a ready-to-use state out of the package and includes a sufficiently low coefficient of friction and stability of the coating adhesion to the medical device, even in instances wherein the medical device and hydrophilic coating are stored in a wetting fluid for an extended period of time.

[0022] The wetting fluid may be a fluid that includes one or more non-polymeric polyols in the amount of from about 5 wt% to about 50 wt% of the wetting fluid. For example, the wetting fluid may include water and between about 10 wt% and about .. 20 wt% of a non-polymeric polyol, such as glycerol. In another embodiment, the amount of non-polymeric polyol may be about 5 wt% of the wetting fluid.

[0023] The wetting fluid, optionally, may contain other additives as well, such as antioxidants, which may be for example tocopherols (vitamin E) or ascorbic acid (vitamin C).
.. [0024] The hydrophilic coatings may be formed from a coating composition that includes a low molecular weight diacrylate compound, such as a diacrylate oligomer, and a hydrophilic polymer. The hydrophilic polymer may be polyvinylpyrrolidone (PVP), polyethylene oxide, methyl cellulose, ethyl cellulose, polyethylene glycol, hydroxyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, polyvinyl alcohol, or mixtures thereof. In one embodiment, the hydrophilic polymer is a polymer having a Mw above 500,000. For example, the hydrophilic polymer may be PVP having a Mw of at least 500,000. In one embodiment the diacrylate compound has a number average molecular weight (Mn) of less than about 1000 or less than about 900, preferably less than 600, more preferably between about 200 and about 600, and even more preferably between about 400 and about 600. The diacrylate compound may be, for example, PEGDA
having a Mn of less than about 1000 or less than about 900. In one embodiment, the PEGDA has Mn of less than about 600. In another embodiment, the PEGDA has Mn of between about 200 and about 600. In yet another embodiment, the PEGDA has a Mn of between about 400 and about 600.

Date recue/Date received 2023-05-29 [0025] The present disclosure also discloses base coat and top coat compositions that may be used to form such hydrophilic coatings. The base coat and top coat compositions may be solutions or dispersions that are applied to the surface of a substrate, and then cured and/or dried to form the base coat and top coat layers of the hydrophilic coating. While the base coat and top coat compositions disclosed herein and coatings formed therefrom are described relative to urinary catheters, the compositions and coatings may be used to coat virtually any substrate for which it is desired to provide a lubricous hydrophilic coating on the surface thereof. The coatings and compositions are particularly useful for medical devices that are intended to be inserted into and removed from the body, such as urinary catheters, endoscopes, drainage catheters, etc.
[0026] The base coat compositions and top coat compositions disclosed herein may be used with one another to form lubricious hydrophilic coatings on a substrate.
While the top coat compositions may be applied over the base coat compositions, a base coat is not required and the top coat compositions may be applied directly to the surface of the substrate to form a hydrophilic coating on the substrate.
In one embodiment, the top coat composition may be applied directly to an untreated surface of a substrate. For example, the hydrophilic composition (top coat) may be applied directly to an untreated surface of a urinary catheter without the use of a base coat or wherein the surface has not been treated with plasma treatment, corona treatment or the like or with a solvent prior to application of hydrophilic composition which forms the hydrophilic coating.
[0027] Turning back the base coat, the base coat may be formed from a blend including a hydrophilic polymer and a diacrylate compound having a number average molecular weight (Mn) of less than about 1000 or less than about 900, preferably less than 600, more preferably between about 200 and about 600, and even more preferably between about 400 and about 600. For example, the base coat layer may be formed from a base coat composition that includes a hydrophilic polymer, and PEGDA oligomer dissolved or dispersed in a solvent. The PEGDA may have a Mn of less than about 1000 or less than about 900. In one embodiment, the PEGDA has Date recue/Date received 2023-05-29 Mn of less than about 600. In another embodiment, the PEGDA has Mn of between about 200 and about 600. In yet another embodiment, the PEGDA has a Mn of between about 400 and about 600.
[0028] The hydrophilic polymer may be, for example, polyvinylpyrrolidone (PVP), polyethylene oxide, methyl cellulose, ethyl cellulose, polyethylene glycol, hydroxyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, polyvinyl alcohol, or mixtures thereof. In one embodiment, the hydrophilic polymer is a polymer having a Mw above 500,000. For example, the hydrophilic polymer may be PVP having a Mw of at least 500,000. In one embodiment of the base coat composition, the PVP may have a Mw of 1.3m as determined by light scattering.
[0029] The base coat composition may also include a curing agent, such as a photoinitiator, which may be for example a type I photoinitiator, such as Irgacure 2959. The base coat composition also includes a solvent, such as water, ethanol, methanol, isopropyl alcohol, propanol or mixtures thereof. The base coat composition may optionally include additives such as antioxidants or antimicrobials.
[0030] In one embodiment, the solid components of the base coat composition in the dry state (without solvent) may include PEGDA in an amount of between about 5 wt% and about 90 wt% of the total solids and a hydrophilic polymer(s) in an amount of between about 10 wt% and about 95 wt% of the total solids. The base coat composition in the dry state may also include a curing agent in the amount of between about 0.1 wt% and about 5 wt% of the total solids. In other embodiments, the solid components in the dry state may include PEGDA in an amount between about 15 wt% and about 25 wt% of the total solids and a hydrophilic polymer(s) in an amount between about 75 wt% and about 85 wt%.
[0031] When the solid components are mixed with a solvent to form the base coat composition, the composition may include PEGDA in an amount between about 0.1 wt% and about 5 wt% of the total composition, an amount of hydrophilic polymer(s) of between about 0.5 wt% and about 10 wt%, an amount of solvent of between about 90 wt% and about 99 wt%, and an amount of curing agent of between about 0.01 Date recue/Date received 2023-05-29 wt% and about 1 wt%.
[0032] In one embodiment, the base coat composition may include:
PEGDA 4.25 g PVP K90 0.75 g Irgacure 2959 0.2 g Ethanol 94.8 ml [0033] In another embodiment, the base coat composition may include:
PEGDA 4.25 g Ethyl Cellulose 10cP 0.75 g Irgacuree 2959 0.2 g Ethanol 94.8 ml [0034] In yet another embodiment, the base coat composition may include PEGDA 4.25 g PVP K90 0.50 g Ethyl Cellulose 10cP 0.25 g Irgacuree 2959 0.2 g Ethanol 94.8 ml [0035] In another embodiment, the base coat composition may include:
PEGDA 4.25 g Ethyl Cellulose 10cP 0.50 g HPM Cellulose 0.25 g Irgacuree 2959 0.2 g DI Water 20.0 ml Ethanol 74.8 ml [0036] The base coat layer may be formed on the surface of a medical device by applying the base coat composition to the surface and then curing and/or drying the base coat composition to form the base coat layer. The base coat compositions may be applied in any suitable manner, such as by dip coating or spraying. The base coat composition may be cured and dried by any suitable manner such as by exposure to UV light.

Date recue/Date received 2023-05-29 [0037] The concentration of the PEGDA in the base coat layer formed from the base coat composition after drying and curing may be less than 85 wt% of the base coat layer. It may also be less than 50 wt% and, in some embodiments, it may be less than 20 wt% of the base coat layer. For example, the base coat layer formed from the composition after drying and curing may include PEGDA in an amount of between about 5 wt% and about 90 wt% of the base coat layer and a hydrophilic polymer in an amount of about 10 wt% and about 95 wt%. In one embodiment, the base coat layer may include PEGDA in an amount between about 80 wt% and about 90 wt% of the base coat layer and the hydrophilic polymer in an amount of between about 10 wt% and about 20 wt% hydrophilic polymer.
[0038] Furthermore, the components of the base coat layer may be immiscible or partially immiscible. In one embodiment, the PEGDA of the base coat layer comprises a discrete, continuous or bi-continuous phase within the coating layer.
The base coat layer may include a phase separated morphology wherein the PEGDA
forms one phase and the hydrophilic polymer forms another phase.
[0039] Turning to top coat layer, the top coat layer may be formed from a blend, such as a top coat composition, that is applied over the base coat layer or directly to a treated or untreated surface of a substrate and then cured to form the hydrophilic coating.
[0040] In one embodiment of the top coat composition, the composition may include a hydrophilic polymer, and any PEGDA of different Mn described above. These components may be dissolved and/or dispersed in a solvent. The top coat composition may also, optionally, include one or more of curing agents, polyelectrolytes, humectants, plasticizers and/or antioxidants.
[0041] The solvent may be any suitable solvent, such as ethanol, methanol, water, isopropyl alcohol or mixtures thereof. Additionally, the PEGDA may have a Mn of less than 1000, or less than 900 or less than 600, or between about 200 and about 600, or between about 400 and about 600.
[0042] When used in the top coat composition, the polyelectrolytes may be, for example, a copolymer with acrylic acid, preferably with acrylamide. The Date recue/Date received 2023-05-29 polyelectrolyte may be polyacrylic acid-co-acrylamide copolymer (PAAc), polyacrylamide-co-methacrylic acid, or polyacrylic acid. The polyelectrolyte composition may have less than 30% by weight of ionizable groups based on total weight of the copolymer. The humectants or plasticizing agents may be, for example, glycerol or polyethylene glycols or any suitable plasticizer that plasticizes or allows the coating to be more flexible. The curing agent may be a Norrish type I or preferably a Norrish type ll photoinitiator, such as benzophenone. The antioxidant may be any suitable antioxidant, such as butyl hydroxytoluene-alcohol (BHT-alcohol).
[0043] In one embodiment, the solid components of the top coat composition in the dry state (without solvent) may include PEGDA in an amount of between about 1 wt%
and about 20 wt% of the total solids, a hydrophilic polymer(s) in an amount of between about 80 wt% and about 98 wt% and a curing agent in an amount of about 0.05 wt% and about 0.5 wt%. The top coat composition in the dry state may also include an antioxidant in an amount of between about 0.05 wt% and about 0.5 wt% of the total solids, a plasticizer in an amount of between about 2 wt% and about wt%, an polyelectrolyte in an amount of between about 1 wt% and about 10 wt%, and/or any other suitable additive. In other embodiments, the solid components in the dry state may include PEGDA in an amount between about 3 wt% and about 6 wt% of the total solids and a hydrophilic polymer(s) in an amount between about 85 wt% and about 90 wt%, and optionally, an amount of antioxidant, plasticizer, polyelectrolyte and/or any other suitable additive up to 10 wt%.
[0044] The top coat composition in the liquid state may include between about wt% and about 10 wt% hydrophilic polymer, between about 0.1 wt% and about 0.6 wt% PEGDA, between about 0.005 wt% and about 0.1 wt% curing agent, and between about 89 wt% and about 97.5 wt% solvent. The top coat composition may, optionally, further include between about .005 wt% and about 0.1 wt%
antioxidant, between about 0.1 wt% and about 1 wt% plasticizers and/or about 0.1 wt%, about wt% polyelectrolyte and/or any other suitable additive. In another embodiment the top coat in the liquid state may include between 4 wt% and 7 wt% hydrophilic polymer, between 0.2 wt% and 0.4 wt% PEGDA between about 0.005 wt% and Date recue/Date received 2023-05-29 0.015 wt% curing agent and about 90 wt% to 95 wt% solvent and optionally, an amount of antioxidant, plasticizer, polyelectrolyte and/or any other suitable additive.
[0045] The top coat composition may be applied over the base coat layer or directly to the treated or untreated surface of the medical device in any suitable manner, such as by dip coating or spraying. The top coat composition may then be cured in any suitable manner to form the top coat layer and the hydrophilic coating. For example, curing of the top coat composition may include curing by exposure to UV light.

[0046] In one embodiment, the dried and/or cured top coat layer formed from the composition may include about 80 wt% to about 95.5 wt% hydrophilic polymer and about 0.5 wt% to about 20 wt% PEGDA. The top coat layer may optionally include about 1 wt% to about 10 wt% plasticizer and/or about 1 wt% to about 10 wt%
polyelectrolyte. In one embodiment, the top coat layer may include hydrophilic polymer in an amount between about 94 wt% to about 98 wt%, PEGDA in an amount between about 2 wt% to about 6 wt% and, optionally, an amount of antioxidant, plasticizer, polyelectrolyte and/or any other suitable additive.
[0047] The components of the top coat layer may be immiscible or partially immiscible. For example, the PEGDA of the top coat layer may be a partially immiscible or an immiscible component. In one embodiment, the PEGDA of the top coat layer comprises a discrete, continuous or bi-continuous phase within the coating layer. The top coat layer may include a multiple phase morphology wherein the PEGDA separates from the hydrophilic polymer phase during drying and curing.
That is, wherein the PEGDA forms one phase and the hydrophilic polymer forms a second phase.
[0048] To form the lubricious hydrophilic coating on a substrate, such as a medical device, the base coat composition, when one is used, is applied to a surface of the substrate, by for example, dip coating, spraying or any other suitable manner.
The base coat is then cured and/or dried by, for example, UV lights or any other suitable manner. In one embodiment, curing and drying the base coat composition results in a base coat layer having a multiple-phase morphology. The top coat composition is then applied over the base coat layer, when one is used, or applied directly to the Date recue/Date received 2023-05-29 treated or untreated surface of the substrate by, for example, dip coating, spraying or any other suitable manner. The top coat composition is then cured and/or dried to form the top coat layer. Curing and/or drying can be done by, for example, exposure to UV light or any other suitable manner. In one embodiment, curing and/or drying of the top coat composition results in a top coat having phase separated components.
[0049] When the coating is formed, the substrate may be packaged in a wet environment wherein the substrate is in direct liquid contact with a wetting fluid containing one or more non-polymeric polyols. The package containing the medical device and the wetting fluid, optionally, may be radiation sterilized by, for example, gamma or E-beam radiation.
EXAMPLES
[0050] Example 1 [0051] Hydrophilic coatings were formed on the outer surfaces of catheters made from polyvinyl chloride (PVC catheters). The catheters had a size of CH14 and a shore hardness of 82A. The hydrophilic coatings included a base coat layer formed on the outer surface of the catheter and a top coat layer formed over the base coat layer.
[0052] Base Coat Composition [0053] The base coat composition was prepared with the components as shown in the table below.
[0054] Table 1 Component Amount Methanol 97.98% (w/w) Polyvinylpyrrolidone K90 (PVP) (Ashland) 1.61%
(w/w) Irgacure 2959 (BASF) 0.01%
(w/w) Polyethylene glycol diacrylate (PEG400DA) (3R344, Sartomer, inhibitor removed) 0.40%
(w/w) [0055] The base coat composition was prepared by slowly adding the PVP to methanol while mixing until the PVP was dissolved. PEG400DA and Irgacuree 2959 were then added and allowed to fully dissolve while the solution was stirred.

Date recue/Date received 2023-05-29 [0056] Top Coat Composition [0057] The top coat composition was prepared with the components as shown in the table below.
[0058] Table 2 Component Amount (w/w) Ethanol (absolute) (Lennox) 78.99% (w/w) De-ionized water (Lennox) 14.00% (w/w) PVP K90 (Ashland) 5.95% (w/w) BHT-A (Sigma Aldrich) 0.01% (w/w) PEG400DA (5R344, Sartomer, inhibitor removed) 0.30% (w/w) Glycerol 0.74% (w/w) Benzophenone 0.01% (w/w) [0059] The top coat composition was prepared by adding PVP to the ethanol and water and mixing until dissolved. The remaining components (glycerol, PEG400DA, BHT-A, and benzophenone) were then added and allowed to fully dissolve under stirring.
[0060] To form the hydrophilic coating on the outer surfaces of the catheters, the catheters were immersed in the base coat composition for a period of 10 seconds and then withdrawn at a rate of 0.7 cm/sec using a Harland PCX coating machine containing UV lamps. The base coat composition was then cured and dried under UV lamps for 45 seconds to form a base coat layer on the outer surface of the catheter. The catheters were then immersed in the top coat composition for 10 seconds and withdrawn at a rate of 0.5cm/sec. The top coat composition was then UV cured and dried under UV lamps for 10 minutes to form the top coat layer, (resulting in the formation of the hydrophilic coating on the catheter).
[0061] After the hydrophilic coating was formed on each of the catheters, the catheters were individually packaged and sealed in foil packs containing 5 ml of wetting fluid wherein the wetting fluid included 89.6 wt% water, 10 wt%
glycerol and 0.4 wt% ascorbic acid. One set (Sample Set A) of the foil packs was exposed to Date recue/Date received 2023-05-29 kGy of E-Beam radiation and another set (Sample Set B) was exposed to 35 kGy of E-Beam radiation.
[0062] The packages were opened and the catheters were removed from the packages and the initial, abraded and ten minute dry-out coefficients of friction (CoFs) of catheters were a tested.
[0063] CoF measurements are an indicator of lubricity and were measured using a Harland Friction Tester Model FTS5500. The CoFs of the catheters were determined by inserting a mandrel into 127 mm section of the coated catheter tube. The tube was then clamped between two pieces of silicone rubber at 100g load wherein the .. silicone rubber had a shore hardness of 60A. The catheter tube with the mandrel inserted therein was pulled through the two pieces of silicone rubber at a speed of 10 mm/s. The force required to pull about 80 mm of the catheter tube through the two pieces of silicone rubber was measured. The CoF value was calculated from the ratio of recorded to applied loads (i.e., the recorded load divided by the applied load) when steady state was reached. The CoF of each type of catheter was measured immediately after opening the package ("initial"), immediately after being abraded ("abraded") and immediately after a ten-minute dry-out time ("dry-out").
[0064] In measuring the abraded CoFs, the catheter, with the hydrophilic coating in a hydrated state, was cycled back and forth 25 times through a hole in a 1 mm thick, silicone pad having a shore hardness of 60A. The hole was just smaller than the outer diameter of the catheter tube and the abrasion took place under water.
Abrading the catheter in this fashion is designed to remove any portions of the coating that is not well adhered to the tubes. After abrasion, the CoF was measured as described above.
[0065] In measuring the ten minute dry-out time CoF, the catheter, immediately after removal from the package was placed in an atmosphere having a temperature of 23 C and a relative humidity of 50% for 10 minutes before measuring the CoF
as described above.

Date recue/Date received 2023-05-29 [0066] Example 1 Results [0067] Coefficient of Friction Measurements [0068] Table 3 shows the average CoFs for the initial, abraded and ten-minute dry-out CoFs for each set of catheters.
[0069] Table 3 E-Beam Initial Abraded 10 Min Sample Set Radiation CoF CoF Dry-out Dose Avg. Avg. Avg.
A 45 kGy 0.012 0.018 0.027 35 kGy 0.014 0.016 0.018 [0070] Example 2 [0071] The hydrophilically coated catheters of Example 2 were coated with the same base and top coats as described in Example 1 and by the same coating procedures. After the hydrophilic coating was formed on each of the catheters, the catheters were individually packaged and sealed within a foil pack containing 5 ml a wetting fluid. The wetting fluid was one of following:
[0072] Table 4 Wetting Fluid Wetting Fluid Components Sample 100% deionized water (DI water) 99 wt% DI water: 1 wt% Ascorbic Acid 90 wt% DI water: 10 wt% Ascorbic Acid 89.6 wt% DI water: 10 wt% Glycerol: 0.4 wt% Ascorbic Acid [0073] After the packages were sealed, the packages were exposed to a dose of about 30-35 kGy of gamma radiation. The packages were then opened and the catheters were removed from the packages and the initial and abraded CoFs of catheters were a tested using the above described procedures.
[0074] Example 2 Results [0075] Coefficient of Friction Measurements [0076] Table 5 shows the average CoFs for the initial and abraded CoFs for each set of catheters.

Date recue/Date received 2023-05-29 [0077] Table 5 Initial Abraded Wetting Fluid CoF CoF
Sample Avg. Avg.
0.013 0.104 0.030 0.264 0.012 0.064 0.016 0.027 [0078] Dye uptake tests were conducted on the catheters to assess the level of adhesion/non-adhesion between the hydrophilic coatings and catheters. After the CoFs of the abraded catheters were measured, the catheters were dried-out (dehydrate). The dried-out catheters were then immersed in a water soluble red dye for 2 minutes. The catheters were then visually inspected to determine if the dye had been uniformly taken up throughout the coating or if sections of the coated portion of the catheter were dye-free. A uniform dye uptake throughout the coated portion of the catheter indicates that the hydrophilic coating has good adhesion to the catheter.
If the coated portion of the catheter has undyed sections, this is an indication that the hydrophilic coating or sections thereof have significantly thinned and/or separated from the catheter due to lack of adhesion to the catheter.
[0079] Fig. 1 shows the results of dye test conducted on the abraded catheters that were wetted with Wetting Fluid Samples C-F.
Example 3 [0080] The surfaces of catheter tubes made of thermoplastic elastomer (TPE) with a 83 shore hardness were coated with the lubricious top coat formation and top coat application process as described in Example 1 without the use of a base coat or surface treatment being applied to the catheter tube surface prior to coating, i.e., the surface of the catheter tube did not undergo any plasma treatment, corona treatment or the like or any surface cleaning with a solvent prior to applying the top coat formulation. The coated catheter tubes were placed into foil pouches containing 5mL
of wetting fluid. The wetting fluid included 89.6 wt% water, 10 wt% glycerol and 0.4 wt% vitamin C. After ten days, the catheter tubes were sterilized using e-beam radiation at a dose of 45 KGy. The sterilized catheter tubes were removed from the Date recue/Date received 2023-05-29 foil pouches the initial, dry out and abraded Cofs were measured.
[0081] Dye uptake tests were conducted on the catheters to assess the level of adhesion/non-adhesion between the hydrophilic coatings and catheters. After the CoFs of the abraded catheters were measured, the catheters were dried-out (dehydrate). The dried-out catheters were then immersed in a water soluble red dye for 2 minutes. The catheters were then visually inspected to determine if the dye had been uniformly taken up throughout the coating or if sections of the coated portion of the catheter were dye-free. A uniform dye uptake throughout the coated portion of the catheter indicates that the hydrophilic coating has good adhesion to the catheter.
.. If the coated portion of the catheter has undyed sections, this is an indication that the hydrophilic coating or sections thereof have significantly thinned and/or separated from the catheter due to lack of adhesion to the catheter.
Example 3 Results [0082] Coefficient of Friction Measurements [0083] Table 6 shows the average CoFs for the initial, abraded and ten-minute dry-out CoFs for catheters of Example 3.
[0084] Table 6 Initial Abraded 10 Min CoF CoF Dry-out Avg. Avg. Avg.
0.015 0.020 0.032 [0085] Fig. 2 shows the results of dye test conducted on the catheters tubes of Example 3.
Comparative Example 1 [0086] The surfaces of catheter tubes made of thermoplastic elastomer (TPE) with a 83 shore hardness were coated with the below lubricious top coat formation without the use of a base coat or surface treatment being applied to the catheter tube surface prior to coating. The top coat formation was applied using the same top coat application process as described in Example 1.

Date recue/Date received 2023-05-29 [0087] Table 7 Component Amount (grams) PVP K90 (Ashland) 13g Glycerol 0.8g Esacure one (Lamberti) 0.13g Ethanol/Water Mixture 85:15 215g by weight [0088] The coated catheter tubes were placed into foil pouches containing 5m L
of wetting fluid. The wetting fluid included 89.6 wt% water, 10 wt% glycerol and 0.4 wt% vitamin C. After ten days, the catheter tubes were sterilized using e-beam radiation at a dose of 45 KGy. The sterilized catheter tubes were removed from the foil pouches the initial, dry out and abraded Cofs were measured.
[0089] Dye uptake tests were conducted on the catheters to assess the level of adhesion/non-adhesion between the hydrophilic coatings and catheters. After the CoFs of the abraded catheters were measured, the catheters were dried-out (dehydrate). The dried-out catheters were then immersed in a water soluble red dye for 2 minutes. The catheters were then visually inspected to determine if the dye had been uniformly taken up throughout the coating or if sections of the coated portion of the catheter were dye-free. A uniform dye uptake throughout the coated portion of the catheter indicates that the hydrophilic coating has good adhesion to the catheter.
If the coated portion of the catheter has undyed sections, this is an indication that the hydrophilic coating or sections thereof have significantly thinned and/or separated from the catheter due to lack of adhesion to the catheter.
[0090] Comparative Example 1 Results [0091] Coefficient of Friction Measurements [0092] Table 8 shows the average CoFs for the initial, abraded and ten-minute dry-out CoFs for catheters of Comparative Example 1.
[0093] Table 8 Initial Abraded 10 Min CoF CoF Dry-out Avg. Avg. Avg.

Date recue/Date received 2023-05-29 0.038 0.126 0.024 [0094] Fig. 3 shows the results of dye test conducted on the abraded catheters tubes of Comparative Example 1. The sterilized coatings of Comparative Example showed a degradation of the coating performance after hydration and eBeam .. sterilization at 45KGy following abrasion.
[0095] It will be understood that the embodiments described above are illustrative of some of the applications of the principles of the present subject matter.
Numerous modifications may be made by those skilled in the art without departing from the spirit and scope of the invention, including those combinations of features that are individually disclosed herein.

Date recue/Date received 2023-05-29

Claims

CLAIMS:

1. A catheter assembly comprising:
a package defining a cavity;
a medical device including a hydrophilic coating located within the cavity, the hydrophilic coating including a hydrophilic polymer and low molecular diacrylate and wherein the hydrophilic coating has been formed directly on an untreated surface of the medical device; and a wetting fluid comprising one or more non-polymeric polyols located within the cavity and in contact with the hydrophilic coating.

2. The assembly claim 1, wherein the medical device comprises a urinary catheter.

3. The assembly of any one of claims 1 and 2, wherein the one or more non-polymeric polyols comprises one or more of Glycerol, Erythritol, Threitol, Arabitol, Xylitol, Adonitol, Mannitol, Sorbitol, Galactitol, Fucitol, lditol, lnositol, Volemitol, lsomalt, Maltitol, Lactitol, Maltotriitol, and Maltotetraitol.

4. The assembly of any one of claims 1-3, wherein the one or more non-polymer polyols comprises Glycerol.

5. The assembly of any one of claims 1-4, wherein the one or more non-polymeric polyols is between about 5 wt% and about 50 wt% of the wetting fluid.

6. The assembly of any one of claims 1-5, wherein the one or more non-polymeric polyols is between about 10 wt% and about 20 wt% of the wetting fluid.

7. The assembly of any one of claims 1-5, wherein the one or more non-polymeric polyols is about 5 wt% of the wetting fluid.
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8. The assembly of any one of claims 1-7, wherein the low molecular weight diacrylate comprises polyethylene glycol diacrylate.

9. The assembly of claim 8, wherein the number average molecular weight of the polyethylene glycol diacrylate is less than 600.

10. The assembly of any one of claims 8-9, wherein the polyethylene glycol diacrylate has a number average molecular weight between about 200 and about 600.

11. The assembly of any one of claims 8-10, wherein hydrophilic coating comprises about 80 wt% to about 95.5 wt% hydrophilic polymer and about 0.5 wt%
to about 20 wt% polyethylene glycol diacrylate.

12. The assembly of any one of claims 8-10, wherein the hydrophilic coating comprises about 94 wt% to about 98 wt% hydrophilic polymer and about 2 wt% to about 6 wt% polyethylene glycol diacrylate.

13. The assembly of any one of claims 8-12 wherein the hydrophilic coating comprises the polyethylene glycol diacrylate as a partially immiscible or an immiscible component.

14. The assembly of any one of claims 8-13 wherein the polyethylene glycol diacrylate comprises a discrete, continuous or bi-continuous phase within the coating.
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